BACKGROUND AND
OBJECTIVES: Tako-Tsubo syndrome is a rare postoperative complication with
a 5% mortality rate. The objective of this report was to present residual neuromuscular
blockade as a trigger for this syndrome, discuss this disorder, and call attention
to the risks of residual neuromuscular blockade.CASE REPORT: A 61-year old female, physical status ASA I, who underwent
general anesthesia associated with paravertebral cervical block for arthroscopic
repair of a rotator cuff lesion. Physical exam after extubation detected residual
neuromuscular blockade. In the post-anesthetic care unit the patient developed
somnolence, tachycardia, hypertension, and severe respiratory acidosis. After
reintubation the patient evolved for cardiac arrest with electrical activity
without a pulse, which was reverted with the administration of adrenaline and
external cardiac massage. In the postoperative period the patient presented
elevation of the ST segment, increased troponin, and left ventricular medial-apical
akinesia with an estimated ejection fraction of 30%. Cardiac catheterization
showed absence of significant atheromatous lesions in the coronary vessels,
and severe disruption of the systolic function with inferior and antero-septo-apical
akinesia and compensatory basal hypercontractility. The patient had complete
functional recovery with the treatment instituted.CONCLUSIONS: Residual neuromuscular blockade associated with diaphragmatic
paralysis and possible pulmonary atelectasis leading to respiratory failure,
hypercapnia, and adrenergic discharge triggered the Tako-Tsubo syndrome with
severe clinical repercussion.

Residual neuromuscular
blockade (RNB) is a relatively common complication even with intermediary-acting
neuromuscular blockers 1-7, which has a high morbidity 2,3.
On the other hand, Tako-Tsubo syndrome is a rare postoperative complication8.
This is a transitory systolic myocardial dysfunction affecting the apex of the
left ventricle. In the acute phase, the shape of the heart, during systole,
is similar to a Japanese vase used to trap octopuses (Tako = Octopus, Tsubo
= vase) 9-15, with a 5% mortality rate 14. The objective
of this report was to present a case of RNB triggering the Tako-Tsubo syndrome.

CASE REPORT

A 61-year old female,
physical status ASA I, 65 kg, 1.63 m, was admitted for arthroscopic repair of
a rotator cuff lesion on the right shoulder. Monitoring with electrocardiograph
(DII and V5), pulse oximeter, automatic non-invasive blood
pressure, nasopharyngeal temperature, and capnography/gas analyzer (after intubation)
was instituted. Clonidine, 1 µg.kg-1, and fentanyl, 1 µg.kg-1,
were administered, followed by a paravertebral cervical block (posterior brachial
plexus block) with 20 mL of 1% ropivacaine. After the blockade, which was free
of intercurrences, general anesthesia was induced with 3.8 µg.kg-1
of fentanyl, 1.9 mg.kg-1 of propofol, and 0.76 mg.kg-1
of rocuronium. Sevoflurane (expired fraction of 0.8 to 1%) was used for anesthesia
maintenance. Intraoperative intercurrences were not observed. Dexamethasone,
10 mg, ondansetron, 4 mg, ketoprofen, 100 mg, and dypirone, 2 g, were administered.
At the end of surgery, 75 minutes after induction, the administration of sevoflurane
was discontinued and neostigmine, 46.2 µg.kg-1, and atropine,
23.1 µg.kg-1, were administered. Ninety minutes after anesthetic
induction, with the patient in dorsal decubitus and head elevated 45°, with
expired fraction of sevoflurane of 0.1%, the patient opened her eyes spontaneously.
The patient was extubated and afterwards the physical exam detected RNB (incapable
to sustain her head for 5 seconds). Since she was not complaining of dyspnea
the patient remained in the operating room for about 30 minutes during which
time she was breathing oxygen (6 L.min-1) via a face mask spontaneously,
pulse oximetry varied from 93% to 98%, and she was hemodynamically stable. The
patient was transferred to the post-anesthetic care unit (PACU) approximately
120 minutes after anesthetic induction. The patient became progressively somnolent,
with an increase in blood pressure and heart rate. Arterial blood gas analysis
demonstrated severe hypercapnia (PaCO2 = 101 mmHg). Propofol, 2 mg.kg-1,
was administered and the patient was reintubated 150 minutes after anesthetic
induction. The patient became hypotensive and 15 minutes later she evolved to
cardiac arrest with electrical activity without pulse which was reverted with
1 mg of adrenaline and external cardiac massage.

She was transferred
to the intensive care unit (ICU) intubated and on mechanical ventilation, hemodynamically
stable, awake, and without neurological deficits. Electrocardiogram upon admission
to the ICU revealed elevation of the ST segment from V3 to V6.
Troponin (10 ng.mL-1 - normal < 1.5) and CK-MB (23 U.L-1
- Normal up to 6) were increased. The echocardiogram showed akinesia of the
left ventricular walls with an ejection fraction of 30% and the following conclusion:
left ventricular ischemic cardiomyopathy with important disruption in systolic
function. Cardiac catheterization showed severely disruption in systolic function,
with antero-septo-apical and inferior akinesia and compensatory hypercontractility
of the basal portions (left ventricular apical ballooning), and coronary arteries
free of significant atheromatous diseases (Figures 1 and
2). The patient showed good response to 10 µg.kg-1.min-1
of dobutamine and was extubated 22 hours after anesthetic induction. Her condition
improved progressively, and she was discharged from the hospital on 4 mg of
candesartan, and outpatient follow-up by the cardiologist. She had complete
recovery of the functional capacity, and an echocardiogram done 30 days after
discharge from the hospital showed normal contractility of the left ventricle,
with an ejection fraction of 63%, allowing the discontinuation of the medication.
The patient does not have recollections of the day of the surgery.

DISCUSSION

Tako-Tsubo Syndrome
is extremely rare, but it might have been underdiagnosed since it was described
recently (1990) 9. It has also been called transitory ventricular
apical ballooning syndrome. It affects mainly women (6:1) above 60 years of
age, postmenopausal, without history of cardiac disease 10-15. The
presentation in the majority o cases is suggestive of acute myocardial infarction
(AMI), and this is typically the initial diagnosis. Electrocardiographic (elevation
of the ST segment + inversion of the T wave) and cardiac enzymes (troponin and
CK-MB) changes lead to this diagnosis 8. Left ventricular dysfunction
with low ejection fraction on echocardiogram contributes for this diagnosis.
However, coronary lesions that could justify the diagnosis of AMI are not seen
in the hemodynamics laboratory, and ventriculography shows an image typical
of this syndrome (Chart I) 16. Its
pathophysiology is not well defined. The main hypotheses include microvascular
spasm and direct myocardial damage caused by catecholamines from adrenergic
receptors 13. Most cases are related with a phenomenon that generates
severe physical or emotional stress (e.g., death in the family, exacerbation
of chronic systemic diseases, or invasive procedure). It can cause, among other
complications, pulmonary edema, cardiogenic shock, and atrial and ventricular
fibrillation 8. It has a good prognosis after the acute phase, and
ventricular recovery is seen in two to three weeks. Recurrences are rare.

Diagnostic criteria
(Chart I) confirmed the diagnosis of Tako-Tsubo
syndrome in the case presented here. Besides, she has the most common profile
of patients who develop this syndrome, and her evolution was typical: initial
clinical signs suggestive of AMI, cardiac catheterization showed absence of
coronary artery lesions, ventriculography showing an image characteristic of
this syndrome, and good evolution with complete recovery.

The cardiac arrest
with pulseless electrical activity developed by the patient was probably secondary
to a combination of the following factors: severe ventricular dysfunction caused
by the Tako-Tsubo syndrome, aggravated by respiratory acidosis, reduced myocardial
contractility, vasodilation triggered by propofol, and interruption of the existing
adrenergic discharge. Immediate return of normal sinus rhythm after the administration
of adrenaline makes it unlikely that involvement of other causes of cardiac
arrest, such as: pulmonary thromboembolism, pneumothorax, anaphylaxis, hypercalemia,
and hypovolemia related to prolonged resuscitation maneuvers. The brief period
of cardiac arrest and elevated inspired fraction of oxygen explain neurological
recovery without sequelae.

Tako-Tsubo syndrome
is secondary to severe sympathetic discharge triggered by physical or emotional
stress. It is likely that both were present in the case presented here. The
fact that the patient did not recall what happened and the absence of dyspnea
do not exclude the possibility of severe emotional stress. The association of
the residual effect of anesthetic drugs, prostration secondary to hypercapnia,
and cardiac arrest could explain the amnesia. On the other hand, the patient
was under physical stress triggered by hypercapnia, which was reflected on the
tachycardia and hypertension that seem to be the main factors responsible for
the development of this syndrome.

Cases of Tako-Tsubo
syndrome secondary to respiratory difficulty, such as asthma exacerbation, spontaneous
pneumothorax, and after bronchoscopy have been reported 8,14. In
the present case, respiratory difficulty was a consequence of associated factors
that caused severe hypoventilation. Paralysis of the diaphragm was the first
factor. Although it was not diagnosed by an imaging exam (ultrasound, radioscopy,
or chest X-ray), we think that it was present due to its high prevalence (up
to 100%) after high brachial plexus blocks 17.

Residual neuromuscular
blockade, diagnosed clinically, was the second factor. The main clinical tests
include elevation of the head for 5 seconds, hand squeeze, elevation of the
legs from the surgical bed, and maintenance of the tongue between the incisive
teeth. They are accompanied by a wide variation on the train-of-four (TOF) and,
due to their limitations, should be used with caution. Even with T4/T1 ratios
to TOF as low as 0.5, a patient is capable of maintaining the head elevated
for 5 seconds and to show a strong hand grip 18. Respiratory function
monitors also do not indicate the return of muscular function, since they reflect
the recovery of centrally-located muscles, especially the diaphragm 18.
Due to the reasons exposed here, monitoring with acceleromyography would have
been important, not only for the diagnosis of RNB, but also for its quantification.

Despite the seemingly
adequate reversal of the neuromuscular blockade with anti-cholinesteratic agents,
the rate of RNB after the use of intermediate-action neuromuscular blockers
is considerable (8 to 9%), when one considers a minimal T4/T1 ratio to TOF >
0.719. Since a growing consensus suggests that full recovery only
happens with T4/T1 > 0.9, this incidence tends to be even more elevated 19.
Although one cannot exclude the importance of the clinical evaluation of RNB,
this can only be ruled out with objective methods that provide a quantitative
measure of neuromuscular recovery 20. More important that the evidence
of RNB in this case, monitoring would have been fundamental for the diagnosis
of deep neuromuscular blockade that was not readily reversible. Due to the lack
of monitoring, the neuromuscular blockade was not reversed at the appropriate
time or the correct dose for the degree of the blockade was not used, resulting
in RNB when the patient awakened. In the absence of TOF stimulation one should
wait instead of stimulating the reversal of the neuromuscular blockade21.
In the presence of only one or two stimuli, the dose of neostigmine to revert
the blockade is 70 µg.kg-1. In the presence of three or four
stimuli, a dose of 40 µg.kg-1 is adequate. In the presence of
RNB after reversion, a complementary dose of neostigmine was indicated, and
the patient should have been reintubated immediately with persistence of the
RNB, but, in the present case, it was done later 18.

Pulmonary atelectasis
was the third possible factor. Despite not being diagnosed, it should be considered
since it is a frequent complication, especially in the presence of RNB and paralysis
of the diaphragm.

Therefore, one
should remember the importance of monitoring the neuromuscular function, and
RNB as a cause of morbidity, especially if associated with other factors that
cause respiratory difficulties. In the case presented here, the association
of RNB, paralysis of the diaphragm, and possible pulmonary atelectasis, led
to respiratory insufficiency, hypercapnia, and adrenergic discharge, triggering
the onset of Tako-Tsubo syndrome and its clinical repercussions.